Hormonal Contraception and HIV: Weighing the Evidence and Balancing the Risks

Editor’s note: This article was updated at 7:02 pm on Thursday, October 6th to correct the second paragraph, which originally implied that Heffron was the first author on the study on pregnancy and HIV risk. The first author actually is N.R. Mugo.

An article in yesterday’s New York Times by Pam Belluck suggesting that injectable contraceptive use might double the risk of HIV transmission among women and their partners sent a wave of anxiety through the global public health community. The story is based on a study conducted in Africa by Renee Heffron and her colleagues and published online this week in The Lancet. Heffron’s study suggests that HIV-negative women using injectable contraception might face a two-fold risk of acquiring HIV from their infected partners, and that HIV-positive women using injectable contraceptives may be twice as likely to pass the virus on to their uninfected partners.

Another analysis of these same data found that pregnancy itself doubles the risk of transmitting HIV and that pregnancy also doubles the risk of acquiring HIV (largely because of differences between pregnant and non-pregnant women in age, contraceptive use, and sex without condoms).

If the findings on injectable contraceptives are confirmed through further research, the implications are profound. Women make up 60 percent of those infected with HIV in sub-Saharan and are highly vulnerable to HIV infection for a range of economic, social, and biological reasons. Women are simultaneously at high risk of death and disability from complications of pregnancy and unsafe of abortion. Ending the spread of HIV, filling the unmet need for contraception, and preventing the large number of unintended pregnancies in Africa are critical and highly-intertwined global health goals which, if reached, would save millions of lives and dramatically improve prospects for women and children.

Remove injectable contraceptives from this mix and the picture becomes rather bleak. “The injectable birth control shot has revolutionized women’s access to modern contraception in developing countries,” said Latanya Mapp Frett, Vice President-Global, of Planned Parenthood Federation of America. “This method allows women with infrequent access to health centers to prevent unintended pregnancy, thereby reducing rates of complicated pregnancies, unsafe abortion and maternal death. We need to seriously weigh the evidence before restricting women’s access to this life-saving resource.”

As the Times noted, the World Health Organization (WHO) plans to convene a meeting in January 2012 to review the Heffron study in light of existing evidence and examine the meaning of these findings for delivery of health services.

Thepossibility that one proven and highly effective health intervention–injectable hormonal contraception–is exacerbating another public health crisis is of course cause for deep concern, and raised reasonable questions among advocates as to why WHO would wait until January to convene a meeting on these issues, and whether distribution of injectable contraceptives should be halted immediately.

Experts say: “Not so fast.”

Public health and women’s rights experts are taking the study very seriously but also caution against drawing conclusions from the NYT story in part because it overstated or misrepresented some of the study’s findings while neglecting to mention several potential weaknesses. And because the stakes for women are so high, they also say it is important to take a step back and look at the broader range of evidence on this issue carefully, especially in an era when promotion of evidence-based public health interventions such as family planning and safer sex have become so politicized and misinformation spreads rapidly.

There appears to be consensus among public health experts on three basic steps:

1) Consider the effects of methodological weaknesses in the analysis and whether these may have influenced the conclusions.

2) Weigh this study against the existing evidence and conduct research specifically designed to examine these questions.

3) Balance the risks women face from both HIV and unintended pregnancy.

A discussion of each of these points follows:

1) Examine possible methodological weaknesses.

The Heffron study was originally designed to examine the effectiveness of the antiviral medication acyclovir in preventing HIV infection associated with Herpes simplex virus in both sero-discordant couples (in which one partner is HIV-positive and the other HIV-negative) and concordant couples (in which both partners have the same HIV status). It was not designed to examine the connections between hormonal contraceptives and HIV transmission. Findings on their initial research question were inconclusive so Heffron and her colleagues went back through their data to look for other outcomes including the association between hormonal contraception and HIV transmission.

While evaluating the kinds of data they collected for these outcomes is a highly complicated exercise, reviewers of the paper say the study that resulted is in several ways methodologically stronger than earlier studies examining these questions. The analysis also, however, contains weaknesses that could make the results less conclusive than initially appears to be the case and certainly less than the Times story suggested.

In a research note published in the same volume of the Lancet, Charlies Morrison and Kavita Nanda of the international health organization FHI 360, write:

The main strength of the study is that exposure to HIV was known. The study population consisted of HIV-serodiscordant couples, and analysis was limited to HIV infections genetically linked to the index partner. As such, the study was able to provide direct data on the risk of HIV-infected women using hormonal contraception transmitting the virus to their male partner. By contrast with many other studies, self-reported condom use was similar between hormonal and non-hormonal groups. Finally, the investigators used sophisticated analytical techniques and were able to adjust analyses for the plasma viral load of the infected partner.

However, they also note that:

[S]imilar to all observational studies, this study was open to aetiological pitfalls. Potential selection bias and confounding could have distorted interpretation. Furthermore, like all but two studies on this topic, this study was a secondary analysis of an HIV-prevention trial—not specifically designed to examine hormonal contraception and HIV risk. Few women used hormonal contraceptives (only 196.6 [11%] of the total person-years of follow-up were among hormonal-contraceptive users) and few HIV infections (ten for DMPA and three for oral contraceptives) occured for these users.

In selecting quotes, the Times article glazed over these and other possible limitations of the study, including the fact that contraceptive use was self-reported and not confirmed by the researchers through examination of clinical records. Contraception was not provided in all 14 sites used in the study and therefore not consistent across them. Participants in the study often switched contraceptive methods: Almost half of the women who reported using hormonal contraceptives also used non-hormonal methods at some point, but switching was not taken into account in analyzing the data. All of these are methodological weaknesses that could skew the results.

The Times also over-stated the conclusiveness of findings on condom use. Belluck, for example, wrote:

The researchers recorded condom use, essentially excluding the possibility that increased infection occurred because couples using contraceptives were less likely to use condoms.

This is not accurate. Condom use in the study was self-reported. It is very difficult to accurately measure condom use from self-reporting because people tend to overstate to researchers the consistency with which they use condoms (a well-known phenomenon), and there was no way to measure whether couples in the study reporting condom use actually used condoms during all sex acts, some sex acts and not others, or even consistently and correctly over the three-month period. The researchers did control for condom use but based on data that were not systematically collected to answer these questions. Because of this, Morrison and Nanda note that the researchers’ “analytical adjustment for condom use might be insufficient.” One expert, speaking off the record, suggested that while the findings of this study absolutely require further examination, the analysis of condom use alone was cause for “healthy skepticism” of whether the findings were conclusive.

Also not taken into consideration in the Heffron study and not reflected in the Times article were considerations such as whether women using injectable contraceptives had more frequent sex, which may have been their motivation in seeking out long-acting contraception in the first place. More frequent sex would mean more frequent exposure to unintended pregnancy and its potential complications, but also to HIV from an infected partner, especially in the absence of consistent and correct use of condoms or “dual protection” (contraception for pregnancy prevention and condom use for prevention of infection). Sexual coercion or lack of control over the timing and nature of sex may also leave women more vulnerable to unsafe sex, HIV infection, and unintended pregnancy, and might further confound the analysis.

2) Weigh the evidence.

Experts underscore that while this study should be taken seriously, it does not, according to Heather Boonstra, Senior Public Policy Associate at the Guttmacher Institute, “change the weight of the body of evidence to date, which currently suggests no relationships between hormonal contraception and HIV transmission or acquisition.”

In a guidance memo sent to field offices after the initial presentation of the Heffron study at an AIDS conference ealrier this year, USAID states:

Previous studies have examined these issues. Some found similar associations (including one of the largest studies on this topic); most have not found HC [hormonal contraception] to be associated with HIV acquisition or transmission in a general population. The new [Heffron] findings raise concerns, particularly since the analysis involved a large sample size of serodiscordant couples, used sophisticated statistical techniques, and may provide biological support by measuring viral shedding.

Still, continues the memo, “a cautious interpretation of the findings is justified as the scientific community gathers additional information. Like previous analyses, these findings were derived from observational data, which may be biased by self-selection.”

The memo concludes that because there is as yet insufficient information and analysis on the study and its implications, “USAID does not believe that a change in contraceptive policy or programming is appropriate or necessary at this time” and stated it will:

continue to offer a wide variety of contraceptive methods, and ensure that women and couples have access to a wide variety of contraceptive methods, are counseled about the known risks and benefits of those methods (including that all methods other than male and female condoms provide no protection from sexually transmitted infections (STIs), including HIV), and are able to select the method that best fits their individual needs.

The WHO meeting in January is intended to bring together a range of experts to look at this and previous data in as many as 12 other studies, and examine the body of evidence as a whole.

Virtually everyone agrees that carrying out systematic research examining as a primary question the possible connections between hormonal contraception and HIV infection should be a high priority.

3) Balance the Risks.

In the lives of women in sub-Saharan Africa, nothing involving sex and reproduction is “risk free.” In low-resources settings characterized by extremes of gender bias, the combined lack of consistent access to basic family planning methods, prenatal care, trained birth attendants and emergency obstetric care all make pregnancy a dangerous undertaking. Lack of access to family planning to prevent unintended pregnancy and lack of access to safe abortion services mean millions of women each year suffer dire consequences trying to exert some control over their lives. Lack of control over sex and reproduction contribute to both high rates of unintended and unwanted pregnancies, and to high rates of HIV infections.

Injectable contraceptives are widely used in sub-Saharan Africa in large part because these methods give women control over whether and when to become pregnant. Approximately 12 million women between the ages of 15 and 49–six percent of all women in this age group–depend on this method. If it is found that use of hormonal contraception does indeed increase the risk of acquriing or transmitting HIV infection, we are faced with the potential loss of a major public health intervention. Removing the method from the mix of options leaves women vulnerable to different but also dangerous risks from unintended pregnancy, which may also increase their risk of HIV infection, or unsafe abortion or both.

Irrespective of whether conclusions from the Heffron study stand up to further research and examination, there is are no easy answers.

Still, to some degree, some answers are already clear.

First, at the most basic level, it is critical to the health and lives of women and their families to expand, not reduce, access to essential family planning services, continue to improve the quality of services, and continue to underscore the critical nature of dual prevention strategies, via the use of effective methods of contraception combined with correct and consistent condom use, including both male and female condoms. Expanding integrated family planning and HIV prevention services is also critical and can not be over-emphasized. Unprotected sex can lead to both unintended pregnancy and to HIV infection. We know how to prevent both, but we must both invest in these services while ending the stigma associated with safer sex practices.

Second, we need to invest more in expanding the range of reproductive technologies. “What the debate over this study underscores more than anything is the need for more methods that protect couples from both unintended pregnancy and HIV,” said Vanessa Cullins, MD, Vice President of Medical Affairs at PPFA. “Until these products are developed, women and their partners need better access to condoms; and they should not have their birth control taken away.”

Third, we must greatly expand efforts to promote and secure the rights of women, economically, socially, and culturally. High rates of maternal mortality and illness, and high rates of HIV infection among women are but symptoms of the broader social illness rooted in gender discrimination, gender-based violence, and the lack of investment in health, education, and economic power of women and girls. Only when women’s health needs are made a priority by every government everywhere, and when women can exercise their rights will we eradicate HIV and make maternal morality a very rare event.

I absolutely agree with your analysis that it is critical to the health and lives of women to expand, access to family planning services, invest more in expanding reproductive technologies and to promote and secure the rights of women, economically, socially, and culturally, these answers are certain and have been for a long time. Without question we need the answer to many other questions that these findings call for. For example, how safe is deep in pill or patch formulations. I want to know how the women who may have become infected because of injectable hormonal contraceptive have to say.

Most of the experts you site are not the ones that have suffered or will suffer the consequences if indeed there is no doubt that depo makes women more vulnerable to infection or that the risk is greater than what was thought. The expertise we need to hear more of, is that which, comes from life experience.

We have reports from women living with HIV that are sexual reproductive rights advocates working on the problem of coercive use of hormone injectables that this risk for the drug has been known for a long time. There are many women in Africa that want access to the product stopped and more definitive research of the risk and research on how many women got infected.

I hear what you are saying about unintended pregnancies and clearly we need better options to all safe contraceptives. I cannot help but wonder if this “let’s wait and see” reaction, from many, would be the same if this kind of news impacted North America as much as it impacts Africa.

Beri Hull

Global Advocacy Officer

The International Community of Women Living with HIV

jodi-jacobson

I am so glad you wrote and hope you will write a piece on the issues you raise.

I wanted to respond to a couple of points. One is that I do not think there is any “wait and see” attitude but rather the focus is, as I understand it, on developing research that focuses on these questions. The Heffron study did not focus on these questions; it was designed for another purpose, and these conclusions were drawn retrospectively. You can not ignore the findings, but you also can not make policy on them because there are too many possible confounding factors. For example, the fact that both Depo AND pregnancy created the same risk (2-fold) of HIV infection suggests perhaps something else might be going on… frequency of sex, lack of condom use, etc.

I would be the first person to cry foul if I felt like there were other agendas here. I just do not in this case.

I do believe there are multiple risks women on the ground and experiencing these situations in their lives–these Hobson’s choices–and we need to address all of them, mitigate all of them, but we need to do so based on real evidence. we don’t want to take away one public health intervention if we don’t have to do so; we must find alternatives if in fact this proves true.

We know that women’s bodies are controlled in many ways: they may want contraception and be refused it, they may want abortion and be refused it, they may want to be sterilized and be refused; on the flip side, we know when governments and institutional actors want to do so they may also abrogate rights by, as you have pointed out elsewhere, sterilizing wmen without their consent or forcing a trade of one set of rights for another.

We know women need, for example, integrated health services that give them access to HIV prevention and family planning… yet powerful forces have opposed this.

What I want to see is research gearted toward answering the questions about links with Depo, or any other method, and what can replace those. I have no reason to doubt that those with whom I have spoken want the same.

I am really glad you wrote and let’s keep this conversation going and push for the kinds of research needed.

Jodi

j-heck

Thanks for a more full report on the recent study published in The Lancet. One thing,

surely you mean “maternal mortality” and not maternal morality in the last sentence at the end of your blog?